Efficient Construction of Biaryls and Macrocyclic Cyclophanes via Electron-Transfer Oxidation of Lipshutz Cuprates

Abstract

An efficient method for the homocoupling of aryl halides by electron-transfer oxidation of Lipshutz cuprates (Ar2Cu(CN)Li2) with organic electron acceptors is disclosed. Thus, various types of Lipshutz cuprates are prepared by successive treatment of aryl or heteroaryl bromides with tert-butyllithium and CuCN. The electron-transfer oxidation of Lipshutz cuprates with p-benzoquinones proceeds smoothly to afford the corresponding homocoupling products in moderate to good yields. Furthermore, it can be applied to the construction of either thiophene- or benzene-fused 10-membered ring cyclophanes. For the synthesis of 10-membered cyclophanes, the linear C-Cu-C structure of Lipshutz cuprates should be maintained in the dimetallacyclic intermediates, producing the large ring cyclophanes efficiently. The X-ray analysis of the cyclophanes reveals that the difference in the bridging atoms results in the different conformations of the macrocyclic rings. Thus, the silicon-bridged cyclophane 5a adopts a D2-symmetric structure with a twisted rhombic arrangement of four thiophene rings, whereas the methylene- and oxygen-bridged cyclophanes 5b and 5c possess C2h- and C2-symmetric structures with chair- and boatlike conformations, respectively. The 1H NMR spectrum of C2-symmetric 5c is temperature-dependent, and the activation energy (DeltaG) for the conformational change is 10.1 kcal/mol.

Efficient homocoupling reactions of halide compounds catalyzed by manganese (II) chloride

“…[23] This compound was prepared from 1g and the catalytic system [24] This compound was prepared from 1h and the catalytic system [25] This compound was prepared from 1i and the catalytic system MnCl 2 -Mg to give the product as a white solid after column chromatography with hexane.…”

Catalytic Asymmetric Bromine‐Lithium Exchange: A New Tool to Build Axial Chirality

“…With our best catalyst in hand (14) we investigated somewhat more its properties (catalyst loading or alkyllithium reagent) under these standard conditions ( Table 2).…”

Copper‐Mediated Aryl‐Aryl Couplings for the Construction of Oligophenylenes and Related Heteroaromatics

“…In addition, this methodology can be successfully applied to the construction of macrocycles 54. [52] Although the macrocyclizations such as intramolecular ring closure and intermolecular cyclooligomerization generally afford macrocyclic products in low yields owing to the preferable formation of linear oligomers and 5-and 6-membered rings in some cases, our novel ET oxidation of metallacyclic intermediates including the Lipshutz cuprates 53 results in the formation of macrocyclic dimers owing to the preferable formation of a dimetallacyclic intermediate with a linear Ar-Cu(I)-Ar arrangement.…”

“…[52] Since this new coupling can be expected to have a wide applicability to the synthesis of large-membered oligophenylenes, we employed this procedure for the synthesis of 71a and its hexaalkyl derivatives 71b-71d. We also expected the formation of the dodecaphenylenes 72b-72d, because the ET oxidation of Lipshutz cuprates tends to form larger cyclic oligomers than the CuCl 2 -mediated homocoupling reaction of di-Grignard derivatives.…”

“…[51] For the synthesis of the nonaphenylenes 71 and the dodecaphenylenes 72 ( Figure 5), we next carried out the ET oxidation of Lipshutz cuprates, because this reaction is a very strong tool for the formation of aryl-aryl bonds. [52] Thus, the reaction of 73a-73e with 4 equivalents of t-BuLi at À78 8C, followed by treatment with 1 equivalent of CuCN in THF (for 73a) or ether (for 73b-73e) at À78 8C to room temperature produced the corresponding Lipshutz cuprates 75 and 76.…”